ModraDoc006/Ritonavir Offers Promising Therapeutic Option for mCRPC, Convenient Approach Amid COVID-19 Pandemic
February 8, 2021
Dr. Ulka N. Vaishampayan
ModraDoc006, a novel oral docetaxel formulation, has advantages as a convenient, oral, and better-tolerated potential therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC) when combined with ritonavir (ModraDoc006/r; Abstract 132).
ModraDoc006/r given twice a day, once weekly was compared with 75 mg/m2 of intravenous docetaxel on a 21-day cycle. Initially, 30 mg of ModraDoc006 combined with 200 mg of ritonavir in the morning and 20 mg of ModraDoc006 with 100 mg of ritonavir in the evening were administered on days 1, 8, and 15 of the 21-day cycle. After 39 patients, ModraDoc006 was lowered to 20 mg twice daily to reduce gastrointestinal toxicities; the ritonavir dosing remained the same.
At the data cut-off of November 30, 2020, 44 patients had been randomly assigned to intravenous docetaxel and 46 to ModraDoc006/r, with 58 patients currently on treatment. Preliminary prostate-specific antigen (PSA) response rates and radiographic progression-free survival (rPFS) rates were comparable in both treatment arms. ModraDoc006/r was mainly associated with mild and reversible gastrointestinal toxicity, of which grade and incidence were reduced when the dose level of ModraDoc006 was adjusted to 20/20 mg. Myelosuppression and neurotoxicity were low to negligible in the ModraDoc006/r arm, with low accompanying levels of infection and alopecia.
“The data yielded a surprisingly positive toxicity profile, with no cytopenias and no neuropathy noted in the patients treated at the 20/200 ModraDoc006/r dose,” said the study’s lead investigator, Ulka N. Vaishampayan, MD, of the University of Michigan.
All patients received 5 mg of oral prednisone twice a day. Imaging was obtained every 8 to 9 weeks for the first 24 weeks, and every 12 weeks thereafter. Initially, patients with mCRPC with RECIST 1.1 measurable disease were eligible; this was amended to evaluable disease per Prostate Cancer Working Group 3 (PCWG3) to allow for wider recruitment. No prior taxane therapy was allowed.
The primary efficacy endpoint was rPFS per PCWG3 criteria. Secondary objectives included objective response rate, PSA-PFS, time to skeletal-related events, disease control rate, duration of response, and safety. Patient-reported outcomes, quality of life, and Functional Assessment of Cancer Therapy–Prostate questionnaires were assessed. Investigators have noted preliminary clinical efficacy of ModraDoc006/r therapy in mCRPC. A sample size of approximately 50 evaluable patients per arm will provide a point estimate of the primary endpoint of rPFS for this study.
“Adverse events of cytopenias and alopecia were lower with ModraDoc006/r, and preliminary efficacy appears comparable in both arms,” Dr. Vaishampayan said. “An oral chemotherapy option has become critically important during the COVID-19 pandemic, and preliminary data reveal that ModraDoc006/r is an attractive oral option in the treatment of mCRPC, with a favorable toxicity profile and comparable efficacy.”
“An oral chemotherapy option has become critically important during the COVID-19 pandemic, and preliminary data reveal that ModraDoc006/r is an attractive oral option in the treatment of mCRPC, with a favorable toxicity profile and comparable efficacy.” – Dr. Ulka N. Vaishampayan
Dr. Vaishampayan noted that the risk of infection from cytopenias and neuropathy is a frequent hurdle to the use of intravenous docetaxel in the treatment of mCRPC. She said these data hold promise for the drug development of this agent and will provide an additional option, especially for patients with mCRPC who cannot currently tolerate intravenous docetaxel.
“It will also save on the infusion time, which has emerged as a critical issue during the COVID-19 pandemic,” Dr. Vaishampayan said.
Noting that the study demonstrated that ModraDoc006/r presents a convenient, oral, and better-tolerated potential therapeutic option for patients with mCRPC, she hopes it will “enable further investigation of ModraDoc006/r and support further development to make the drug available as an option for every patient with mCRPC.”
Dr. Vaishampayan added that the availability of this agent will expand the application of chemotherapy to older patients with significant comorbidities and has the potential to help improve outcomes in mCRPC. She believes it will have a positive impact on the morbidity of this disease and will provide an oral tolerable chemotherapy option for patients with mCRPC.
Additional data will be presented during a Poster Session at the upcoming 2021 Genitourinary Cancers Symposium.
–Geraldine Carroll
Masofaniten +Enzalutamide This could be a game changer...Science is coming to our aid
Update to Can't treat what we can't see
Anyone prescribe Metformin for prostate cancer not for diabetes? 
